1. Academic Validation
  2. miR-181b-5p inhibits endothelial-mesenchymal transition in monocrotaline-induced pulmonary arterial hypertension by targeting endocan and TGFBR1

miR-181b-5p inhibits endothelial-mesenchymal transition in monocrotaline-induced pulmonary arterial hypertension by targeting endocan and TGFBR1

  • Toxicol Appl Pharmacol. 2020 Jan 1;386:114827. doi: 10.1016/j.taap.2019.114827.
Haiyan Zhao 1 Yang Wang 2 Xiaoli Zhang 1 Yingying Guo 1 Xiaofei Wang 3
Affiliations

Affiliations

  • 1 Department of Immunology and Rheumatology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
  • 2 Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, People's Republic of China.
  • 3 Department of Immunology and Rheumatology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China. Electronic address: [email protected].
Abstract

Endothelial-mesenchymal transition (EndMT) is a frequent event in endothelial dysfunction, which is associated with pulmonary arterial hypertension (PAH). MiR-181 family members exert diverse effects in multiple biological processes. However, the relationships between miR-181b-5p (miR-181b) and EndMT in PAH are not well understood. In this study, Sprague-Dawley (SD) rats were injected with monocrotaline (MCT) to establish PAH model, and primary rat pulmonary arterial endothelial cells (rPAECs) were treated with TNF-α, TGFβ1 and IL-1β in combination to induce EndMT (I-EndMT). Then we explored miR-181b expression and examined its functional role in PAH. Our data showed that miR-181b was down-expressed in PAH, and its overexpression attenuated the hemodynamics, pulmonary vascular hypertrophy, right ventricular remodeling and EndMT process in MCT-induced PAH rats. In I-EndMT rPAECs, we observed that inducing miR-181b reversed the decrease of endothelial markers and increase of mesenchymal markers. However, knockdown of miR-181b induced similar effects to EndMT. In addition, endocan and TGFBR1 levels were also increased in EndMT, which were negatively regulated by miR-181b. Luciferase activity results indicated that endocan and TGFBR1 were direct target genes of miR-181b. In summary, our findings firstly demonstrate that the beneficial effect of miR-181b on PAH may be associated with endocan/TGFBR1-mediated EndMT, providing a new insight into the diagnosis and treatment of PAH.

Keywords

Endocan; Endothelial-mesenchymal transition; Pulmonary arterial hypertension; TGFBR1; miR-181b-5p.

Figures
Products